We have found that the administration of estradiol and progesterone to the ovariectomized rat results in enhanced trypsin-like activity in uterine chromatin capable of breaking down histones and increasing RNA synthesis. We plan to isolate the enzyme(s) using affinity chromatography and study its properties. The activity will be looked for in the human in conditions related to estradiol-progesterone stimulation. These include endometrium obtained at hysterectomy during the luteal phase of the cycle and hormone-dependent tumors, obtained at surgery. In animal studies, the effect of specifically inhibiting this proteolytic activity will be assessed. We have developed a method for the assay of the 4 major estriol conjugate in body fluids of human pregnancy. We plan to continue to apply the method to the simultaneous assay of blood and urine so that the renal clearance of each conjugate can be calculated. Comparisons will be made with clearances of inulin and PAH. Studies will be done in normal pregnancy characterized by very high or low total plasma estriol levels relative to total urinary levels. Values will be related to the status of the fetus, placenta and mother. Finally we plan to develop a radioimmunoassay for 15 alphs-hydroxyestrone-15-N-acetylglucosaminide. We have evidence that this and related sub#tances are synthesized by the human fetus. The levels in the amniotic fluid may provide valuable information concerning the status of the fetus. Analyses will be done on fluids drawn for the routine determination of lecithin/sphingomyelin ratios.